Montagner, Diego and Tolan, Dina and Andriollo, Emma and Gandin, Valentina and Marzano, Cristina (2018) A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells. International Journal of Molecular Sciences, 19 (12). p. 3775. ISSN 1422-0067

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Abstract

In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitumor potential than the reference drug cisplatin. In addition, an antitumor potential of 1 was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cells. Mechanistic studies performed in colon cancer cells confirmed that the conjugation of chlorambucil to Pt(IV) cisplatin-based scaffold tunes the lipophilicity of the prodrug, consequently improving the ability of the compound to accumulate into cancer cells and to target DNA, ultimately leading to apoptotic cancer cell death.

Item Type:	Article
Additional Information:	© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Cite as: Montagner, D.; Tolan, D.; Andriollo, E.; Gandin, V.; Marzano, C. A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells. Int. J. Mol. Sci. 2018, 19, 3775.
Keywords:	cisplatin; chlorambucil; Pt(IV) prodrugs; cytotoxicity;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	10749
Identification Number:	https://doi.org/10.3390/ijms19123775
Depositing User:	Diego Montagner
Date Deposited:	25 Apr 2019 14:21
Journal or Publication Title:	International Journal of Molecular Sciences
Publisher:	MDPI
Refereed:	Yes
URI:	https://www.mdpi.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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